This double blinded, placebo-controlled study will evaluate the efficacy of long-term suppressive therapy w/oral acyclovir in infants w/neonatal herpes simplex virus infections limited to the skin, eyes, and mouth (SEM) disease. It will determine if suppressive oral acyclovir therapy improves neurologic outcome in infants following SEM disease. Also, it will address the significance of a positive cerebral spinal fluid (CSF) polymerase chain reaction (PCR) result when all other CSF parameters remain normal. The PCR test looks directly for the virus in the CSF. Comparisons will be made between groups w/respect to time post-randomization to first positive CSF PCR results during the initial 12 months of life, and results will be correlated w/clinical neurological assessment. It will determine if continuous administration of acyclovir suspension suppresses recurrent skin lesions in infants following SEM disease, and it will confirm the safety of long-term administration of oral acyclovir therapy in a cohort of infants w/SEM disease. Finally, the effects of suppressive acyclovir therapy on issues of pharmacoeconomics and family infrastructure will be assessed and quantitated. Neurologic impairment at 12 months of life. Neurologic development will be assessed by the Bayley Scales of Infant Development-Revised for ages 0-3yrs, and by the Wechsler Preschool and Primary Scales of Intelligence-Revised (WPPSI-R) for children older than 3yrs of age. When feasible, the Woodcock-Johnson Psycho-Educational Battery-Revised (WJ-R) will also be utilized for evaluation of children older than 3yrs of age (in addition to the WPPSI-P).